It has become quite clear in the last several years that a decrease in the concentration of lung surfactant (composed primarily of disaturated lecithin) is causally related to respiratory distress syndrome (RSD). By implication, a decreased rate of pulmonary lecithin synthesis is the likely pathogenic factor in the disease. The key question of what factors regulate lung surfactant synthesis is being approached by studies on the enzymes of the two pathways of lecithin synthesis and by determining levels of substrates (metabolites) in the pathways. By determining the changes in rate of lecithin synthesis as a function of gestation, the importance of regulatory factors will be determined. The role of corticosteroids in controlling lung maturation and lung lecithin synthesis is being assessed in both fetal and newborn animals. It has been determined that lung lecithin concentration and rate of lecithin synthesis increases during the latter 10-20% of gestation for both fetal rat and rabbit. The principal pathway for lung lecithin synthesis appears to be the choline incorporation route rather than phosphatidyl ethanolamine methylation. Administration of corticosteroids to the fetus enhances the rate of lung synthesis within six hours after injection and increases the activity of choline phosphotransferase (CPT). Corticosterone-deficient decapitated rat fetuses show low lung choline phosphotransferase activity which may be increased to normal within six hours after a physiological dose of dexamethasone. Various kinetic properties of the three enzymes in the choline incorporation pathway have been determined. By full order of magnitude, choline phosphotransferase shows the lowest specific activity of the three enzymes, and thus appears to be the rate-limiting catalyst in the pathway.